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Chapter 11 Pathophysiology of Renal disorders. By Dr. Uche Amaefuna-Obasi (MD) THERE ARE MORE TO LECTURES THAN JUST SLIDES Renal Diseases Introduction: • 150gm: each kidney • 1700 liters of blood filtered 180 L of G. filtrate 1.5 L of urine / day. • Kidney is a retro-peritoneal organ • Blood supply: Renal Artery & Vein • One half of kidney is sufficient – reserve • kidney function: Filtration, Excretion, Secretion, Hormone synthesis. Kidney Location: Kidney Anatomy: Renal Pathology Outline • Glomerular diseases: Glomerulonephritis • Tubular diseases: Acute tubular necrosis • interstitial diseases: Pyelonephritis • Diseases involving blood vessels: Nephrosclerosis • Cystic diseases • Tumors Clinical Syndromes: • Nephritic syndrome. Oliguria, Haematuria, Proteinuria, Oedema. • Nephrotic syndrome. Gross proteinuria, hyperlipidemia, • Acute renal failure Oliguria, loss of Kidney function - within weeks • Chronic renal failure. Over months and years - Uremia Introduction • Functions of the kidney: excretion of waste products regulation of water/salt maintenance of acid/base balance secretion of hormones • Diseases of the kidney glomeruli tubules interstitium vessels Kidneys • Nephron Working unit of the kidney Consists of • Glomerulus: works like a sieve • Tubules: fluid reabsorbed or sent to bladder Kidney Functions • Regulates extracellular fluid & osmolarity, electrolyte concentrations, & acid-base balance • Excretes wastes • Secretes renin • Produces erythropoietin • Converts vitamin D to active form Abnormal findings • Azotemia: BUN (A blood urea nitrogen (BUN) test measures the amount of nitrogen in your blood that comes from the waste product urea. Urea is made when protein is broken down in your body. Urea is made in the liver and passed out of your body in the urine. A BUN test is done to see how well your kidneys are working), creatinine • Uremia: azotemia + more problems • Acute renal failure: oliguria • Chronic renal failure: prolonged uremia Nephrotic syndrome Nephritic syndrome • Massive proteinuria • Hematuria • Hypoalbuminemia • Oliguria • Edema • Azotemia • Hyperlipidemia/-uria • Hypertension Glomerular diseases Nephrotic syndrome •Minimal change disease •Focal segmental glomerulosclerosis •Membranous nephropathy Nephritic syndrome •Post-infectious GN •IgA (immune) nephropathy Nephrotic Syndrome • Massive proteinuria • Hypoalbuminemia • Edema • Hyperlipidemia Causes • Adults: systemic disease (diabetes) • Children: minimal change disease • Characterized by loss of foot processes • Good prognosis Nephrotic Syndrome • Any kidney disorder that results in proteinuria exceeding 3.5 g/day • Cause Any damage to glomeruli increasing their permeability to plasma proteins Nephrotic Syndrome • Possible causes Infections Chemical damage Immunological & hereditary disorders Diabetes mellitus • Clinical findings Proteinuria Low serum albumin Edema Elevated blood lipids Blood coagulation disorders Consequences • Disturbances in protein metabolism • Edema Loss of albumin Sodium retention • Risk of CVD Elevated LDL, VLDL & lipoprotein(a) Loss of blood clotting proteins • Loss of antibodies • Decreased vitamin D-binding protein Lower D & calcium levels • Protein energy malnutrition (PEM) Consequences of Protein Loss © 2007 Thomson - Wadsworth Treatment • Medications • Fat Anti-inflammatory Low saturated fat, drugs, ACE inhibitors, cholesterol, & antihypertensives, refined sugars immunosuppressants, • Sodium lipid-lowering drugs, 2-3 g/day diuretics • Protein & energy 0.8-1.0 grams/day 35 kcalories/kg • Vitamin D & calcium • Multivitamin Nephritic Syndrome • Hematuria • Oliguria, azotemia • Hypertension Causes • Post-infectious GN, IgA nephropathy • Immunologically-mediated • Characterized by proliferative changes and inflammation Post-Infectious Glomerulonephritis • Child after streptococcal throat infection • Immune complexes • Hypercellular glomeruli • Subepithelial humps IgA Nephropathy • Common! • Child with hematuria after (URI) Upper Respiratory Infection • IgA in mesangium • Variable prognosis • Tubular and interstitial diseases Inflammatory lesions • pyelonephritis Pyelonephritis • Invasive kidney infection • Usually ascends from UTI • Fever, flank pain • Organisms: E. coli, Proteus Urinary Tract Infection • Women, elderly • Patients with catheters or mal-formations • Dysuria, frequency • Organisms: E. coli, Proteus Acute pyelonephritis with abscesses Chronic pyelonephritis Drug-Induced Interstitial Nephritis • Antibiotics, NSAIDS • IgE and T-cell-mediated immune reaction • Fever, eosinophilia, hematuria • Patient usually recovers • Analgesic nephritis is different (bad) Acute Tubular Necrosis • The most common cause of ARF! • Reversible tubular injury • Many causes: ischemic (shock), toxic (drugs) • Most patients recover Benign Nephrosclerosis • Found in patients with benign hypertension • Hyaline thickening of arterial walls • Leads to mild functional impairment • Rarely fatal Malignant nephrosclerosis • Arises in malignant hypertension • Hyperplastic vessels • Ischemia of kidney • Medical emergency Malignant Hypertension • 5% of cases of hypertension • Super-high blood pressure, encephalopathy, heart abnormalities • First sign often headache, scotomas • Decreased blood flow to kidney leads to increased renin, which leads to increased BP! • 5y survival: 50% Adult Polycystic Kidney Disease • Autosomal dominant • Huge kidneys full of cysts • Usually no symptoms until 30 years • Associated with brain aneurysms. Adult polycystic kidney disease Childhood Polycystic Kidney Disease • Autosomal recessive • Numerous small cortical cysts • Associated with liver cysts • Patients often die in infancy Childhood polycystic kidney disease Medullary Cystic Kidney Disease • Chronic renal failure in children • Complex inheritance • Kidneys contracted, with many cysts • Progresses to end-stage renal disease • Tumors Renal cell carcinoma Bladder carcinoma Renal Cell Carcinoma • Derived from tubular epithelium • Smoking, hypertension, cadmium exposure • Hematuria, abdominal mass, flank pain • If metastatic, 5y survival = 5% Renal cell carcinoma Bladder Carcinoma • Derived from transitional epithelium • Present with painless hematuria • Prognosis depends on grade and depth of invasion • Overall 5y survival = 50% Acute renal failure Acute renal failure represents a rapid decline in renal function leading to increased blood levels of nitrogenous wastes and impaired water and electrolyte balance, and manifesting water intoxication, azotemia, hyperkalemia, and metabolic acidosis. Acute Renal Failure • Function rapidly deteriorates Reduced urine output Build up of nitrogenous wastes • Mortality rates are high Acute renal failure is reversible if the cause can be identified and corrected before permanent kidney damage has occurred. The most common indicator is azotemia, which is an accumulation of nitrogenous wastes (urea nitrogen, uric acid and creatinine) Etiology and classification Prerenal failure Intrarenal failure Postrenal failure Causes • Prerenal Heart failure Shock Blood loss • Intrarenal Infections Toxins Drugs Direct trauma • Postrenal Factors preventing excretion of urine Urinary tract obstructions Prerenal failure- functional failure Prerenal failure is the most common form of acute renal failure. It is caused by a marked decrease in renal blood flow. Causes •Hypovolemia •Heart failure •Intrarenal vasoconstriction •Increased blood vessel bed Intrarenal failure- parenchymal renal failure Intrarenal failure results from conditions that can cause damage to structures within the kidney, glomerular, tubular and interstitial. Causes Acute tubular necrosis (ATN) Prolonged renal ischemia (ischemic ATN) or ischemia-reperfusion injury Toxic insult of tubules by drugs, heavy metals (nephrotoxic ATN) Intratubular obstruction hemoglobin and myoglobin severe hypokalemia, hypercalcemia Acute glomerulonephritis and acute pyelonephritis Postrenal failure – obstructive renal failure Obstruction of urine outflow from the kidneys. (ureter, bladder and urethra) Prostatic hypertrophy (most common) Consequences • Oliguria < than • Uremia 400 mL urine/day BUN, creatinine & uric acid accumulate in • Sodium retention blood • Elevated Fatigue, lethargy, potassium, confusion, headache, phosphate, & anorexia, metallic taste, N & V, diarrhea magnesium • Edema Treatment • Drug therapy Diuretics Potassium exchange resins Insulin, glucose Bicarbonate • Protein Depends on kidney function, degree of catabolism, use of dialysis • Fluids Measure output and add 500 mL Can increase if on dialysis • Electrolytes Restrict potassium, phosphorus, sodium Chronic Renal Failure • Is a gradual & • Causes irreversible Diabetes mellitus 43% deterioration Hypertension 26% • Usually not Inflammatory, diagnosed until immunological, or 75% of function is hereditary lost diseases May follow acute failure Consequences • Nephrons enlarge to compensate • Overburdened nephrons degenerate • End-stage renal disease occurs • Evaluation Glomerular filtration rate (GFR) Rate at which kidneys form filtrate Consequences • Electrolyte imbalances occur when GFR becomes extremely low Hormonal adaptations are inadequate Intake of water & electrolytes are very restrictive or excessive • Renal osteodystrophy Increased parathyroid hormone contributes to bone loss • Acidosis may develop • Uremic syndrome Mental dysfunctions Neuromuscular changes Muscle cramping, twitching, restless leg syndrome • Protein energy malnutrition Complications of Uremic Syndrome • Impaired hormone synthesis • Impaired hormone degradation • Bleeding abnormalities • Increased cardiovascular disease risk • Reduced immunity Treatment • Goal Slow disease progression Prevent or alleviate symptoms • Drugs Antihypertensives Erythropoietin Phosphate binders Sodium bicarbonate Cholesterol-lowering medications Active vitamin D supplements Dialysis • Removes excess fluid & wastes from blood • Blood is circulated though a dialyzer • Blood is bathed by dialysate • Hemodialysis & peritoneal dialysis Medical Nutrition Therapy • Energy Enough to maintain healthy weight & prevent wasting • Low-protein diet Can increase when on dialysis • Lipids Restrict saturated fat & cholesterol • Fluids Not restricted until output decreases • Sodium Mild restriction • Potassium May need to restrict highpotassium foods Medical Nutrition Therapy • Calcium & vitamin D needs increase • May need phosphorus restrictions Restrict protein Restrict milk & milk products • Dietary supplements Generous folate and B6 Recommended amounts of watersoluble vitamins except vitamin C IV iron administration • Intradialytic parenteral nutrition Kidney Transplants • Restores function • Allows a more liberal diet • Frees patient from dialysis • Immunosuppressive drug therapy Many side effects affecting nutrition • Protein & energy requirements increase • Control CHO & lipids • Sodium, potassium, & phosphorus intakes liberalized • Calcium supplementation • Be alert for potential food borne infection Kidney Stones • Affects 12% of men & 5% of women • Crystalline mass in urinary tract Severe pain Can obstruct tract • Formation is promoted by: Reduced urine volume Blocked urine flow Increased concentrations of stone-forming substances Types of Stones • Calcium oxalate stones Most common Reduce intake of oxalate Avoid vitamin C supplements • Uric acid stones Abnormally acidic urine Associated with gout Low-purine diet • Cystine stones Inherited disorder cystinuria • Struvite stones Form in alkaline urine Calcium Oxalate Stone Consequences • Renal colic Severe, continuous pain Begins in the back & travels toward bladder Nausea & vomiting • Urinary tract complications Urgency Frequency Inability to urinate Obstruction Infection Prevention & Treatment • Drink 12-16 cups of fluids/day • Tea, coffee, wine, beer • No apple or grapefruit juices Other Dietary Measures • Consume enough calcium to control oxalate absorption • Restrict dietary oxalate & purine • Moderate protein intake • Sodium restriction Dialysis How Does Dialysis Work? • Employs diffusion, • If substance is osmosis, & higher in the ultrafiltration dialysate, substance will • If a substance is diffuse into the lower in dialysate, blood substance will diffuse out of the • Ultrafiltration blood removes fluid from the blood Dialysis • Hemodialysis Lasts 3-4 hours 3 times/week Complications • • • • • • • Infections Blood clotting Hypotension Muscle cramping Headaches, weakness Nausea & vomiting Agitation • Peritoneal dialysis Vascular access not required Fewer dietary restrictions Can be scheduled when convenient • Acute failure Continuous renal replacement therapy (CRRT)
